Racemic Bisindole Alkaloids: Structure, Bioactivity, and Computational Study

Abstract

Main observation and conclusion The new racemic and dimeric indole alkaloids with the characteristic cyclopenta[ b ]indole backbone, (+)‐ and (–)‐spondomine (1a/1b), were isolated from a cultured sponge Tedania anhelans . A semi‐synthesis was employed to obtain 1a/1b and the other four stereoisomers 1c—1f. Their structures were determined by spectroscopic analysis, single‐crystal X‐ray, and quantum chemical calculations. Six stereoisomers differ in bioactivity according to their absolute configurations. Especially, (+)‐spondomine (1a) displayed cytotoxicity against the K562 cell line and exhibited stronger Wnt and HIF1 dual signaling inhibitory activity at 5 μmol/L than the positive control, which offers an exciting starting point for further investigations. All stereoisomers significantly promoted angiogenesis and showed moderate anti‐inflammation in zebrafish. A quantum chemical calculation and deuteration experiment were applied to unveil the reaction mechanism which guides the synthesis of the target compounds.